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Macrophages restrict tumor immune infiltration 3 by controlling collagen topography through a Tcf4-Col3 axis

ABSTRACT: During tumorigenesis, the extracellular matrix is profoundly remodeled. While the impact of such remodeling on tumor growth and invasion is well-described, less is known on its consequences on immune infiltration. Combining tissue imaging and machine-learning, we show that immune cell localization in tumors can be predicted by the local topography of fibrillar collagens. Such topographies are dictated by a fibrotic pathway driven by the transcription factor Tcf4 in both cancer and stromal cells, which promotes collagen 3 deposition, resulting in intermingled collagen networks that favor intra-tumoral infiltration of T cells and neutrophils. Macrophages inhibit this pathway, highlighting their key structural role in shaping the tumor extracellular matrix. Human database analyses revealed a strong correlation between Tcf4, collagen 3, and tumor infiltration by T cells and neutrophils in different solid tumors, attesting the clinical relevance of our findings. Collagen network topographies thus emerge as a major regulator of antitumor immunity .

ORGANISM(S): Mus musculus

PROVIDER: GSE320473 | GEO | 2026/02/26

REPOSITORIES: GEO

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Macrophages restrict tumor immune infiltration 3 by controlling collagen topography through a Tcf4-Col3 axis

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